This project deals with six important areas of clinical bone marrow transplantation (BMT) for hematologic malignancies: (1) We propose to prospectively study in a randomized fashion the efficacy of two novel preparatory regimens in patients with advanced leukemia: One regimen consists of fractionated total body irradiation (FTBI) and high dose etoposide (VP16) and the other one of high dose busulfan (BU) and cyclophosphamide (CY). This study is done as a multi-center trial of Southwest Oncology Group BMT centers. (2) The FTBI/VP16 combination is evaluated in "ideal" BMT candidates, i.e. patients with advanced leukemia in first complete remission (CR) and patients with chronic myelogenous leukemia (CML) in first chronic phase (CP). If this trial results in improved disease free survival as compared to our historical control group which had been treated with FTBI/CY, the FTBI/VP16 combination will be compared prospectively to FTBI/CY. (3) The role of BMT in the management of patients with myelodysplastic or myeloproliferative syndromes will be studied using the BU/CY regimen. (4) We are currently carrying out a dose escalation study of TBI/VP16/CY regimen in patients with advanced lymphoid malignancies (Hodgkin's disease, non-Hodgkin's lymphoma) followed by BMT from histocompatible donors or with autologous marrow (ABMT). After the maximum tolerated dose of this ablative regimen is established, this study will be performed with constant doses in a prospective trial to compare disease free survival after BMT to that following ABMT. (5) To further decrease the incidence of graft-versus-host disease (GVHD), we plan to prospectively evaluate the two drug combinations, cyclosporin (CSA)/prednisone (PSE)/methotrexate versus CSA/PSE. (6) We propose to carry out a prospective study to define the pattern of human cytomegalovirus (HCMV) infection leading to CMV-associated pneumonitis. In addition, we will study the role of (9-(2-Hydroxy-1(Hydroxymethyl) Ethoxymethyl)guanine = DHPG) as a prophylactic anti-CMV agent. Finally, Project I serves as the clinical resource for the experimental projects II-V of this program project grant application. Studies 1, 2, 3 and 5 will be performed jointly at the City of Hope and at Stanford University, studies 4 and 6 will be carried out at the City of Hope only.